Abstract:
:Dysfunction of the endocannabinoid system (ECS) has been identified in metabolic disease. Cannabinoid receptor 1 (CB1) is abundantly expressed in the brain but also expressed in the periphery. Cannabinoid receptor 2 (CB2) is more abundant in the periphery, including the immune cells. In obesity, global antagonism of overexpressed CB1 reduces bodyweight but leads to centrally mediated adverse psychological outcomes. Emerging research in isolated cultured cells or tissues has demonstrated that targeting the endocannabinoid system in the periphery alleviates the pathologies associated with metabolic disease. Further, peripheral specific cannabinoid ligands can reverse aspects of the metabolic phenotype. This Keynote review will focus on current research on the functionality of peripheral modulation of the ECS for the treatment of obesity.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Shrestha N,Cuffe JSM,Hutchinson DS,Headrick JP,Perkins AV,McAinch AJ,Hryciw DHdoi
10.1016/j.drudis.2018.01.029subject
Has Abstractpub_date
2018-03-01 00:00:00pages
592-604issue
3eissn
1359-6446issn
1878-5832pii
S1359-6446(17)30415-4journal_volume
23pub_type
杂志文章,评审abstract::In the last ten years, public online databases have rapidly become trusted valuable resources upon which researchers rely for their chemical structures and data for use in cheminformatics, bioinformatics, systems biology, translational medicine and now drug repositioning or repurposing efforts. Their utility depends o...
journal_title:Drug discovery today
pub_type: 社论
doi:10.1016/j.drudis.2011.07.007
更新日期:2011-09-01 00:00:00
abstract::Benford's law states that the distribution of the first digit of many data sets is not uniform. The first digit of any random number will be 1 almost 30% of the time, and larger digits occur as the first digit with lower and lower frequency, to the point where 9 occurs as a first digit only 5% of the time. Here, we de...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2010.03.003
更新日期:2010-05-01 00:00:00
abstract::Records about the traditional uses of medicinal plants can be considered useful in bioprospecting (i.e., the search for new active agents or lead structures in nature). Several sources like Egyptian papyri, early modern herbals and pharmacopoeias have been studied in this respect. It is proposed to use recordings of b...
journal_title:Drug discovery today
pub_type: 历史文章,杂志文章
doi:10.1016/j.drudis.2016.11.011
更新日期:2017-05-01 00:00:00
abstract::With the aging of the general population, there is an increasing need for bone defect repair, prompting the development of reliable alternatives to autologous bone grafting, without the usually associated major drawbacks (i.e., limited volume and severe postoperative pain). Given the crucial role that miRNAs appear to...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.04.007
更新日期:2017-07-01 00:00:00
abstract::Epigenetic covalent modifications of DNA and chromatin proteins strongly affect gene expression and cellular activity, and epigenetic misregulation occurs in several diseases, especially cancer. First-generation drugs targeting the relatively promiscuous DNA methylation and histone acetylation modifiers have had succe...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.10.010
更新日期:2010-01-01 00:00:00
abstract::Functional proteomics approaches aim to characterize comprehensively the function of gene products, and provide a first-level understanding of cellular mechanisms. Here, we review recent techniques for the construction and prediction of large-scale protein-interaction networks, with a particular emphasis on computatio...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(02)02281-x
更新日期:2002-06-01 00:00:00
abstract::Genomics and gene expression data require interpretation at the protein level to validate the biological or pathological findings. To match with the efficiency and capacity of DNA microarray application, methods and approaches of protein analysis in multiplex and high-throughput manner are required for effectively dis...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(03)02655-2
更新日期:2003-04-15 00:00:00
abstract::To maintain orphan drug status at the time of market authorization, orphan medicinal products (OMPs) need to be assessed for all criteria, including significant benefit, by the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA). Subsequently, health technology assessment (HTA) organi...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2020.04.012
更新日期:2020-07-01 00:00:00
abstract::Nonalcoholic steatohepatitis (NASH) is emerging as a major public health issue for the 21st century and is associated with significant liver-related morbidity and mortality. At present, there are no approved drug therapies for NASH. Consequently, NASH has become the focus of significant public and private research and...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.09.020
更新日期:2019-02-01 00:00:00
abstract::Sudden cardiac death, secondary to ventricular fibrillation (VF), remains the leading cause of death in the USA. Recent experimental and theoretical studies suggest that VF could be caused by spiral wave re-entry. The initiation and subsequent break-up of spiral waves has been linked to electrical alternans, a phenome...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(02)02567-9
更新日期:2003-02-15 00:00:00
abstract::Metabolic determinations are an integral part of every drug-discovery and drug-development program. Recent emphasis has been to increase sample throughput while, at the same time, increase information content within assays. To this end, screening for potential drug-drug interactions, overall metabolic stability and me...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.01.007
更新日期:2007-03-01 00:00:00
abstract::When cross-reactivity of a lead antibody across species is limited, antibody development programs require the generation of surrogate molecules or surrogate animal models necessary for the conduct of preclinical pharmacology and safety studies. When surrogate approaches are employed, the complexities and challenges fo...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.09.014
更新日期:2009-12-01 00:00:00
abstract::With the recent explosion of interest in microarray technology, massive amounts of microarray images are currently being produced. The storage and transmission of these types of data are becoming increasingly challenging. This article reviews the latest technologies that allow for the compression and storage of microa...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03647-0
更新日期:2005-12-01 00:00:00
abstract::The consensus hypothesis on coronary atherosclerosis suggests high LDL-C levels as the major cause and pursues it as the therapeutic target, explicitly assuming: (i) tunica intima of human coronaries consists of only one cell layer - endothelium, situated on a thin layer of scarcely cellular matrix; and (ii) subendoth...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.05.017
更新日期:2016-10-01 00:00:00
abstract::For the past decade, the development of genomic technology has revolutionized modern biological research and drug discovery. Functional genomic analyses enable biologists to perform analysis of genetic events on a global scale and they have been widely used in gene discovery, biomarker determination, disease classific...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.05.005
更新日期:2009-08-01 00:00:00
abstract::Cancer and arthritis present an enormous challenge to society. They share pathogenic pathways that involve extracellular matrix degradation, tissue invasion, and inflammation. Most cancer and arthritis treatments affect normal cell function to cause significant adverse effects in patients. Specific pathways that promo...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.07.009
更新日期:2019-01-01 00:00:00
abstract::The p53 family proteins are among the most appealing targets for cancer therapy. A deeper understanding of the complex interplay that these proteins establish with murine double minute (MDM)2, MDMX, and mutant p53 could reveal new exciting therapeutic opportunities in cancer treatment. Here, we summarize the most rele...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.02.007
更新日期:2016-04-01 00:00:00
abstract::Analyzers for in-vitro diagnostic (IVD) testing facilitate the determination of medical information from biological samples. To reach a high quality, the detection reagents have to be dispensed with a high degree of precision and accuracy. A technology change from conventional pipetting systems to contact-free dispens...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2013.06.011
更新日期:2013-11-01 00:00:00
abstract::The tumor vasculature transports oxygen, nutrients and drugs for crucial roles in tumor therapy. Antivascular therapy directly targets existing tumor vessels to reduce blood perfusion and then inhibit tumor growth. Vascular disrupting agents and ultrasound-stimulated microbubble destruction use chemical toxicity and p...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.06.001
更新日期:2017-10-01 00:00:00
abstract::2018 was a remarkable year, both in terms of the number of new molecular entities (NMEs) approved and the organizations developing them. In total, 59 NMEs received a nod from the US Food and Drug Administration (FDA), most of which were approved using a priority or breakthrough designation. Orphan drugs accounted for ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.05.022
更新日期:2019-09-01 00:00:00
abstract::Highlights of the 9th (Biennial) International Congress on TNF-Related Cytokines (30 October-2 November 2002; The Manchester Grand Hyatt, San Diego, CA, USA. ...
journal_title:Drug discovery today
pub_type:
doi:10.1016/s1359-6446(02)02592-8
更新日期:2003-02-01 00:00:00
abstract::Denosumab (Dmab) was the first monoclonal antibody (mAb) approved for the treatment of osteoporosis. It blocks the receptor activator for nuclear factor κB ligand (RANKL) and acts as a potent antiresorptive agent. In contrast to classic antiresorptive agents, Dmab treatment leads to a progressive increase in bone mass...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2020.09.001
更新日期:2020-09-09 00:00:00
abstract::The increasing prevalence of chronic autoimmune-mediated inflammatory diseases (AIMIDs) in ageing western societies is a major challenge for the drug development industry. The current high medical need for more-effective treatments is at least in part caused by our limited understanding of the mechanisms that drive ch...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.11.010
更新日期:2013-04-01 00:00:00
abstract::'Many professional scientists over the years have expressed their thoughts and ideas in poetry.' ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)01556-7
更新日期:2000-10-01 00:00:00
abstract::Natural products have been, and continue to be, a major source of pharmacologically active substances from which drugs can be developed. Currently, tumor necrosis factor-alpha (TNF-alpha) inhibitors from natural origins are being advanced for the treatment of inflammatory disorders. Elevated TNF-alpha synthesis has be...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2006.06.002
更新日期:2006-08-01 00:00:00
abstract::Nonclinical safety testing of new biotherapeutic entities represents its own challenges and opportunities in drug development. Hot topics in this field have been discussed recently at the 2nd Annual BioSafe European General Membership Meeting. In this feature article, discussions on the challenges surrounding the use ...
journal_title:Drug discovery today
pub_type:
doi:10.1016/j.drudis.2013.08.003
更新日期:2013-12-01 00:00:00
abstract::Senescence forms a universal block to tumorigenesis which impacts on all hallmarks of cancer, making it an attractive target for drug discovery. Therefore a strategy must be devised to focus this broad potential into a manageable drug discovery programme. Several issues remain to be addressed including the lack of rob...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.01.019
更新日期:2012-03-01 00:00:00
abstract::The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologi...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2008.02.006
更新日期:2008-07-01 00:00:00
abstract::Kidneys have a major role in normal physiology and metabolic homeostasis. Loss or impairment of kidney function is a common occurrence in several metabolic disorders, including hypertension and diabetes. Chronic kidney disease (CKD) affect nearly 10% of the population worldwide; ranks 18th in the list of causes of dea...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.04.020
更新日期:2017-07-01 00:00:00
abstract::The excessive release of glutamate following brain injury is responsible for the phenomenon of glutamate excitotoxicity, mediated through glutamate receptors, resulting in apoptotic cell death. KDI ameliorates excitotoxicity and regenerates damaged nerve cells. ...
journal_title:Drug discovery today
pub_type: 新闻
doi:10.1016/S1359-6446(05)03617-2
更新日期:2005-10-01 00:00:00